家族性胆囊结石病发病因素研究

Risk factors of familial gallstone disease: study of 135 pedigrees

目的研究遗传和环境因素在家族性胆囊结石病发病中的作用。方法采用问卷调查方式和B超检查了解家系成员的一般情况和发病情况,采集家系成员外周血用于血脂检查。系谱分析胆石病遗传特点并计算遗传度。结果收集135个家系,共695人,胆石病患者370例,发病率53·24%。其中女性发病率(56·66%)明显高于男性(48·23%)(χ2=4·785,P=0·03)。系谱分析发现男女均可患病,无隔代遗传。一级亲属遗传度138%±7%,双生子同病率100%。胆石病组平均体重指数24kg/m2±3kg/m2,显著高于无胆石病组平均体重指数22·7kg/m2±2·9kg/m2(t=4·035,P<0·01)。胆石病组中有糖尿病、高血压、高血脂病史以及喜油腻饮食者明显多于无胆石病组(P均<0·05)。饮酒习惯、抽烟和胃肠道手术史在胆石病组和无胆石病组中差异无统计学意义。胆石病组高密度脂蛋白和载脂蛋白A1水平低于无胆石病组(P均<0·01)。其余血脂指标在胆石病组和无胆石病组中差异无统计学意义。结论(1)家族性胆囊结石病具有常染色体显性遗传特点,遗传因素是发病的基础。(2)性别、肥胖、喜油腻饮食、高血压、糖尿病和高血脂病史是家族性胆囊结石病发病的危险因素。(3)胆石病患者存在脂类代谢异常。

Objective To explore the role of both inheritable and epidemiological factors in the pathogenesis of familial gallstone disease in pedigrees. Methods 135 pedigrees, with 695 members aged ≥ 18 （18-83, with a mean of 50 ± 14）, 282 males and 413 females, including 370 patients, at least one patient existing in every generation, were investigated. Inquiry was carried out to collect the personal and medical history. Physical examination and ultrasonography were conducted. Blood samples were collected to detect the total cholesterol （TCh）, triglyceride （TG）, high-density lipoprotein cholesterol （HDL-Ch）, and apolipoprotein （Apo） A1 and ApoB. The concentration of low-density lipoprotein cholesterol （LDL-Ch） was calculated by the formula： Tch-TG/5 ＋ HDL-Ch. The inheritable characteristics and heritability were analyzed. Results The prevalence of gallstone disease was 53.24%, 56. 66% among the females, significantly higher than that among the males （48.23% , P = 0.03 ）. The heritability in the first-degree relatives was 138% ± 7%, and the concordance rate of monozygotic twins was 100%. The significant risk factors were female gender （P =0.03）, body mass index （P〈0.01） and diet （P〈0.008）. The history of hypertension, hyperlipidemia, and diabetes were correlated to gallstone disease （P = 0. 008, 〈 0.008, and 0.03 respectively）. Serum HDL-Ch and ApoA1 concentrations were lower in the stone group than in the non-stone group （P = 0. 003 and 0. 005 respectively）. There were no significant differences in TCh, TG, LDL-Ch, and ApoB between the 2 groups. Conclusion Genetic factors play a major role in the pathogenesis of familial gallstone disease, characterized by autosomal dominant inheritance. Female gender, obesity, diet, hypertension, hyperlipidemia, diabetes may be the risk factors of gallstone disease. Dyslipidemia is a characteristic of gallstone disease.